The cyclin-dependent kinase inhibitor p27Kip1 interacts with the aryl hydrocarbon receptor and negatively regulates its transcriptional activity

p27(Kip1) functions to coordinate cell cycle progression through the inhibition of cyclin-dependent kinase (CDK) complexes. p27(Kip1) also exerts distinct activities beyond CDK-inhibition, including functioning as a transcriptional regulator. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor with diverse biological roles. The regulatory inputs that control AhR-mediated transcriptional responses are an active area of investigation. AhR was previously established as a direct regulator of p27(Kip1) transcription. Here, we report the physical interaction of AhR and p27(Kip1) and show that p27(Kip1) expression negatively regulates AhR-mediated transcription. p27(Kip1) knockout cells display increased AhR nuclear localisation and significantly higher expression of AhR target genes. This work thus identifies new regulatory cross-talk between p27(Kip1) and AhR.

Automated summary

This study reveals a new regulatory cross-talk between p27(Kip1) and AhR, as p27(Kip1) interacts with AhR to negatively regulate AhR-mediated transcriptional responses. This adds to the existing knowledge that p27(Kip1) is a direct regulator of AhR transcription, providing a more comprehensive understanding of the regulatory interactions between p27(Kip1) and AhR.